To investigate the reprogramming mechanism of cDHPs on the microenvironment of NSCLC and the interaction with IL-35, we combined multi-omics and single-cell sequencing data analysis and found that high expression of IL-35 in tumor tissues of LUAD patients in the TCGA cohort, as well as the amplification of the gene encoding IL-35, were significantly associated with reduced infiltration abundance of CD8+ T cells, DC cells, and neutrophils in TME. The gene discussed is CD8A; the disease is non-small cell lung carcinoma.